NDLI: Outer membrane permeability and beta-lactamase stability of dipolar ionic cephalosporins containing methoxyimino substituents.

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Outer membrane permeability and beta-lactamase stability of dipolar ionic cephalosporins containing methoxyimino substituents.

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Outer membrane permeability and beta-lactamase stability of dipolar ionic cephalosporins containing methoxyimino substituents.

Content Provider	PubMed Central
Author	Nikaido, H. Liu, W. Rosenberg, E. Y.
Abstract	Some enteric bacteria, such as Enterobacter cloacae, can develop high-level resistance to broad-spectrum cephalosporins by overproducing their chromosomally encoded type I beta-lactamases. This is because these agents are hydrolyzed rapidly at pharmacologically relevant, low (0.1 to 1 microM), concentrations, owing to their high affinity for type I enzymes. In contrast, the more recently developed cephalosporins, with quaternary-nitrogen-containing substituents at the 3 position, show increased efficacy against beta-lactamase-overproducing strains and, indeed, have a much lower affinity for type I enzymes. However, the possible contribution of an improved outer membrane permeability in their increased efficacy has not been studied. We found by proteoliposome swelling assays that cefepime, cefpirome, and E-1040 all penetrated the porin channels of Escherichia coli and E. cloacae much more rapidly than did ceftazidime and at least as rapidly as did cefotaxime. Considering that the influx of anionic compounds such as cefotaxime and ceftazidime will be further retarded in intact cells, owing to the Donnan potential, we expect that the newer compounds will penetrate intact cells 2 to 10 times more rapidly than will cefotaxime and ceftazidime. The kinetic parameters of hydrolysis of these agents by E. cloacae beta-lactamase showed that at 0.1 microM, they were hydrolyzed much more slowly than was cefotaxime and at about the same rate as or a lower rate than was ceftazidime. The combination of these two effects explains nearly quantitatively why these newer agents are more effective against some of the beta-lactamase-overproducing gram-negative bacteria.
Starting Page	337
File Format	PDF
ISSN	10986596
e-ISSN	10986596
Journal	Antimicrobial Agents and Chemotherapy
Issue Number	2
Volume Number	34
Language	English
Publisher Date	1990-02-01
Access Restriction	Open
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Infectious Diseases Pharmacology Pharmacology (medical)

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